Waardenburg Syndrome, Type 3 Clinical CharacteristicsOcular Features: Type 3 Waardenburg syndrome has many of the features of other types but with the addition of upper limb anomalies. Dystopia canthorum and a broad nasal root are characteristic. Iris heterochromia is present in some patients. Hypopigmentation may be seen in lashes and eyebrows. Systemic Features: The upper limbs may appear underdeveloped with flexion contractures, fusion of the carpal bones and sometimes syndactyly. A white forelock may or may not be present. The cranial bones may be anomalous and rare patients can have microcephaly with significant mental retardation. Mental function is usually normal though. Occasional patients have cleft palate and/or lip. Hearing loss is of the sensorineural type. Hypopigmented skin patches are sometimes present but not all patients have them. GeneticsThe uniqueness of Waardenburg syndrome types 1 and 3 remains to be established. Mutations in the PAX3 gene are responsible for both types and both have been found in the same family. The phenotype is transmitted in an autosomal dominant pattern in either case but several families have been reported with type 1 WS in parents heterozygous for PAX3 mutations who had a homozygous child with the type 3 phenotype. However, heterozygous individuals with type 3 have also been reported and the relationship of the two types remains unknown. Craniofacial-deafness-hand syndrome(122880) with mutations in PAX3 has many features similar to those found in Waardenburg syndrome type 3 and may or may not be a unique disorder. Pedigree: Autosomal dominantAutosomal recessiveTreatmentTreatment Options: There is no treatment for the syndrome but cochlear implants might be helpful. ReferencesArticle Title: Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome Wollnik B, Tukel T, Uyguner O, Ghanbari A, Kayserili H, Emiroglu M, Yuksel-Apak M. Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome. Am J Med Genet A. 2003 Sep 15;122A(1):42-5. PubMed ID: 12949970 Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I) Hoth CF, Milunsky A, Lipsky N, Sheffer R, Clarren SK, Baldwin CT. Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I). Am J Hum Genet. 1993 Mar;52(3):455-62. PubMed ID: 8447316 Upper limb involvement in the Klein-Waardenburg syndrome Goodman RM, Lewithal I, Solomon A, Klein D. Upper limb involvement in the Klein-Waardenburg syndrome. Am J Med Genet. 1982 Apr;11(4):425-33. PubMed ID: 7091186 Read more about Waardenburg Syndrome, Type 3
Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome Wollnik B, Tukel T, Uyguner O, Ghanbari A, Kayserili H, Emiroglu M, Yuksel-Apak M. Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome. Am J Med Genet A. 2003 Sep 15;122A(1):42-5. PubMed ID: 12949970
Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I) Hoth CF, Milunsky A, Lipsky N, Sheffer R, Clarren SK, Baldwin CT. Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I). Am J Hum Genet. 1993 Mar;52(3):455-62. PubMed ID: 8447316
Upper limb involvement in the Klein-Waardenburg syndrome Goodman RM, Lewithal I, Solomon A, Klein D. Upper limb involvement in the Klein-Waardenburg syndrome. Am J Med Genet. 1982 Apr;11(4):425-33. PubMed ID: 7091186
